A controlled study of additional sr-L-dopa in L-dopa-responsive restless legs syndrome with late-night symptoms

OBJECTIVE: To investigate whether a combination treatment of regular-release levodopa (rr-L-dopa) and sustained-release levodopa (sr-L-dopa) compared with monotherapy of rr-L-dopa improves sleep quality and reduces periodic limb movements (PLM) in patients with restless legs syndrome (RLS) and problems with maintaining sleep. BACKGROUND: Reappearance of RLS symptoms during the second half of the night while being treated with rr-L-dopa is a common problem in the treatment of sleep disturbances caused by RLS. METHODS: A randomized, controlled, double-blind crossover trial was undertaken. Eligible patients fulfilled the diagnostic criteria of the International RLS Study Group, and met an actigraphically confirmed higher number of PLM per hour time in bed (PLM index) during the second half compared with the first half of the night under treatment with rr-L-dopa. During the crossover periods the patients received 100 to 200 mg rr-L-dopa plus either placebo or 100 to 200 mg sr-L-dopa at bedtime for 4 weeks each period. RESULTS: Thirty patients with RLS (11 men and 19 women) were assessed by actigraphy and subjective sleep quality, and showed a significant improvement in PLM index (p < 0.0001), in "time in bed without movements" (p < 0.0001), and in subjective sleep quality (p < 0.001). Eight of 30 patients reported an altered pattern of RLS symptoms, characterized by a time shift of RLS symptoms into the afternoon or evening, five of these during monotherapy with rr-L-dopa. CONCLUSIONS: A combination therapy of rr-L-dopa and sr-L-dopa is better than monotherapy with rr-L-dopa in reducing the frequency of PLM and problems maintaining sleep, even in patients who are severely affected.     

Polysomnographic sleep measures in patients with uremic and idiopathic restless legs syndrome

In the present study, the nocturnal electroencephalographic sleep pattern, the number of periodic leg movements (PLM) during sleep and wakefulness, and the subjective sleep parameters of patients with uremic (n = 10) and idiopathic (n = 17) restless legs syndrome (RLS) were compared. The main finding was that the total number of PLM (p = 0.019), the PLM index (p = 0.018), and the PLM index while awake (p = 0.003) were significantly higher in patients with uremic RLS compared with patients who had idiopathic RLS. Additionally, both groups showed a distinct time-of-night pattern of PLM activity. Polysomnographic measures of sleep continuity (total sleep time, sleep efficiency, sleep onset latency, time awake) and sleep architecture (amount of nonrapid eye movement sleep stages 1, 2, 3, and 4 and the amount of rapid eye movement sleep) did not differ between uremic and idiopathic RLS patients. With regard to subjective parameters, sleep quality was estimated to be worse in uremic RLS (p = 0.033), whereas other parameters (for example, severity of RLS, quality of life) did not differ between the two groups. It is suggested that uremia itself worsens the motor symptoms of RLS, probably as a result of increased excitability.     

Heel pain and calcaneal spurs

The purpose of the present study was to evaluate sleep patterns and complaints, and Periodic Limb Movement (PLM) and the Restless Legs Syndrome (RLS) in subjects with complete spinal cord injury. Volunteers were submitted to two polysomnograms (Oxford Medilog SAC system--EEG, EMG, EOC): (1) basal night, when the volunteer arrived at the Sleep Center, and (2) after a maximal physical test (Cybex Met 300/increase of 12.5 watts/2 min until exhaustion). Eleven volunteers with complete spinal cord injury between T7-T12 were evaluated. Data were analyzed by the paired Student's test (total sleeping time) and by the Wilcoxon matched paired test (change of sleep states, number of awakenings during sleep, latency to REM sleep and leg movements--PLM + RLS). Comparison of sleep recordings from the night before with that from the night after (12 h) practice of physical activity, showed a significant reduction in all of the sleep parameters. The results indicate that physical activity improves the sleep patterns of spinal cord injured volunteers. In particular, we noticed that PLM and RLS after physical activity were inhibited during sleep.     

Relationships between nocturnal activity, parental ratings of daytime activity and measues from the Children's Sleep Behaviour Scale.

Monitored the nocturnal activity levels of 20 boys and 20 girls (mean age 10.46 yrs) from 12:00 AM to 6:00 AM over 2 consecutive nights in their homes. Frequency of sleep-related behaviors based on retrospective parental ratings was assessed by the Children's Sleep Behavior Scale (CSBS). Children who were rated high on sleep behaviors with an observable motor component were also more active during the night, thereby validating the motor subscale of the CSBS. Nocturnal activity was associated with another CSBS-derived sleep score that included items with positive affective content, such as laughing and smiling while asleep. Children who showed bedtime resistance behaviors and complained of difficulty going to sleep were not more active during the night. Gender, age, and parental perception of daytime activity levels were not related to objective measures of nocturnal activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dynamics of EEG spindle frequency activity during extended sleep in humans: relationship to slow-wave activity and time of day

The dynamics of EEG spindle frequency activity (SFA; spectral power density in the 12.25-15.0 Hz range) and its relationship to slow-wave activity (SWA; 0.75-4.5 Hz) were investigated in long sleep episodes (> 12 h). Young healthy men went to bed at either 19:00 h (early sleep; prior waking 36 h, n = 9) or 24:00 h (late sleep; prior waking 17 h, n = 8). In both nights, SWA in non-rapid-eye-movement sleep (NREMS) decreased over the first three to four 1.5-h intervals and remained at a low level in the subsequent five to six 1.5-h intervals. In contrast, the changes of SFA were more variable and differed between the lower (12.25-13.0 Hz), middle (13.25-14.0 Hz) and higher frequency bin (14.25-15.0 Hz). A pronounced influence of time of day was present in the lower and higher SFA bin, when the dynamics were analyzed with respect to clock time. In both the early and late sleep condition, power density in the lower bin was highest between 2:00 and 5:00 h in the morning and decreased thereafter. In the higher bin, power density was low in the early morning hours and increased as sleep was extended into the daytime hours. The results provide further evidence for a frequency-specific circadian modulation of SFA which becomes more evident at a time when SWA is low.     

Changes in EEG power density during sleep laboratory adaptation

First- and second-night effects on the electroencephalogram (EEG) were investigated by means of polygraphic sleep recordings and all-night spectral analysis. Eighteen normal subjects were studied for three consecutive nights in a hospital sleep laboratory. Visual sleep scoring showed that there was a first-night effect in normal subjects similar to that reported previously [increased wakefulness; decreased total sleep time, sleep efficiency, and rapid eye movement (REM) sleep]. Spectral analysis of the sleep EEG revealed important changes, most of which occurred in REM sleep. Increased delta, theta, and beta1 power densities accompanied by decreased mean frequency were seen in REM sleep in the second night. On the basis of REM sleep deprivation results previously published, our data suggest that the second night could be affected by partial REM sleep deprivation that occurred in the first night. Delta and theta power density values decreased in the first non-rapid eye movement episode of nights 1 and 2; this could result from increased REM sleep pressure. The overall consistency of spectral data in the first and second night with REM sleep findings derived from visual scoring in the first night lends further support to this hypothesis. The sleep disturbance experienced during the first night in a sleep laboratory may be a useful and valid model of transient insomnia. Therefore, we conclude that data from all nights recorded should be included in assessing a subject's sleep.     

Acute dissociation after 1 night of sleep loss.

Recent research has shown that dissociative symptoms are related to self-reports of deviant sleep experiences. The present study is the 1st to explore whether sleep loss can fuel dissociative symptoms. Twenty-five healthy volunteers were deprived of sleep for 1 night. Sleepiness and dissociative symptoms were assessed every 6 hr. The authors measured both spontaneous dissociative symptoms and dissociative symptoms induced by dot-staring during sensory deprivation. Sleepiness as well as spontaneous and induced dissociative symptoms were stable throughout the day but increased during the night. These findings provide further evidence for a robust relationship between disruptions in sleep patterns and dissociative symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationships between thyroid hormone and antidepressant responses to total sleep deprivation in mood disorder patients

BACKGROUND: Acute transient antidepressant effects of sleep deprivation are consistently observed in 50% of depressed patients, but the mechanisms of these, at times, dramatic improvements in mood have not been adequately elucidated. Some, but not all, studies suggest a relationship to increased thyroid-stimulating hormone (TSH) secretion. METHODS: TSH and other thyroid indices were measured at 8:00 AM after a baseline night's sleep and at 8:00 AM following a night of total sleep deprivation (S.D.) in 34 medication-free, affective disorder patients assessed with Hamilton, Beck, and Bunney-Hamburg depression ratings as well as two hourly self-ratings on a visual analog scale. RESULTS: Compared with baseline, S.D. induced highly significant increases in TSH, levothyroxine, free levothyroxine, and triiodothyronine. The 12 S.D. responders tended to have greater TSH increases than the 15 nonresponders (p < .10). The change in Beck depression ratings significantly correlated with the change in TSH (r = -.40, p = .0496, n = 24). CONCLUSIONS: These data are consistent with several other reports of a significant relationship between degree of antidepressant response to S.D. and increases in TSH measured at 8:00 AM near their usual nadir. Acute removal of the sleep-related break on the hypothalamic-pituitary-thyroid axis remains a promising candidate for the mechanism of sleep deprivation-induced improvement in mood in depressed patients.     

Model of a miniature pig catheterized for pharmacokinetic and pharmacodynamic studies of anti-infective agents

The purpose of this study was to examine the role of sleep problems in the etiology of nursing caries. Two-hundred mothers of children (104 with nursing caries and 96 caries free) from ages 2 to 4.5 years were surveyed to determine whether difficulty with child sleep and ensuing sleep-associated feeding might be related to the presence of nursing caries. Differences were noted between these two groups regarding: average number of nights the child slept through the night (P < 0.001); total hours of sleep per night (P < 0.05); frequency of night waking episodes (P < 0.01); feeding on demand upon waking (P < 0.01); using a bottle to assist with falling asleep at night (P < 0.001); and feeding in association with nap time (P < 0.001). Differences also were noted in regard to average age of weaning (P < 0.001). Our findings suggest that sleep problems among young children are a behavioral risk factor for night-time bottle use and early childhood caries.     

Nighttime waking in children with asthma: An exploratory study of daily fluctuations in family climate.

Children with asthma are at increased risk for waking in the night, and there is the potential for the entire household to feel the effects. The authors conducted a telephone-based diary study to examine whether daily fluctuations in parent mood, parenting hassles, and family routines would distinguish nights in which waking occurred from nights in which they did not. Forty-seven families with a child with asthma were contacted 4 times a week every 3 months over a period of 1 year, resulting in 500 daily observations. Parent negative mood, perceived parenting hassles, and disruptions in bedtime routines were associated with increased odds that the child would wake in the middle of the night. Results underscore the importance of considering family climate in children's disturbed sleep. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep deprivation in inpatient treatment of depression. A report of experiences

Sleep deprivation or "stay awake"-therapy), given in addition to drug therapy, is seen as an effective anti-depressive treatment with actually no side effects. Nevertheless, it is not regularly and systematically used. A reason for this might be doubts about its feasibility in psychiatric hospitals without specialised depression wards. Only a few reports exist on the practical aspects of sleep deprivation. The present article informs about the "stay awake"-therapy on 101 depressive patients (in the mean 25 patient-nights per month), carried out at the Psychiatric Hospital Sanatorium Kilchberg/Zurich. The patients (age between 19 and 76, mean 47 years) participated on average in 4.4 partial sleep deprivations. 72% participated at least for a set of three nights. One staff person takes care of a group of at most five patients. Indication, organisation, night programme, care and possible strains are reported. A stay awake night (three times a week) consists of breakfast, games, conversations, taking two walks, and discussions about depression and about treatment (psychoeducation), with the aim to avoid naps and to provide a pleasant social event. The experiences made with serial partial sleep deprivation are encouraging.     

The effect of one night's sleep deprivation on temperature, mood, and physical performance in subjects with different amounts of habitual physical activity

Eleven healthy males were studied twice. On one occasion (control, C), they slept (night 1) and then underwent a battery of tests at 4 h intervals from 06:00 day 1 to 02:00 day 2; then, after a normal sleep (night 2), they were tested from 10:00 to 22:00 on day 2. On the second occasion (sleep deprivation, SD), the subjects remained awake during night 1. Each battery of tests consisted of measurements of tympanic membrane temperature, profile of mood states (POMS), muscle strength, self-chosen work rate (SCWR), perceived exertion, and heart rate (HR) while exercising on a stationary cycle ergometer. Subjects also kept a diary of their activities during the two days and answered a questionnaire about their habitual physical activity. Results showed a significant negative effect of sleep deprivation on most mood states on day 1, but no effect on the other variables. By day 2, mood had tended to recover, though muscle strength tended to be worse in both control and sleep-deprivation experiments. There was also a more general tendency for negative effects to be present at the end of day 1 (02:00) or at the beginning of day 2 (10:00). There was limited support for the view that subjects who were habitually more active showed less negative effects after sleep deprivation and responded less adversely to the poor sleep achieved on the university premises (night 2). These results stress the considerable interindividual variation in the responses to sleep loss and, therefore, the difficulty associated with giving general advice to individuals about work or training capability after sleep loss.     

Urinary 6-sulfatoxymelatonin cycle-to-cycle variability

For either clinical or research purposes, the timing of the nocturnal onset in production of the urinary melatonin metabolite 6-sulfatoxymelatonin (UaMT6s-onset), has been proposed as a reliable and robust marker of circadian phase. However, given that most circadian rhythms show cycle-to-cycle variability, the statistical reliability of phase estimates obtained from a single study using UaMT6s-onset remains to be determined. Following 2 weeks of sleep diary and wrist actigraphy, 15 young, healthy good sleepers participated in four UaMT6s sampling sessions spaced 1 day apart. During the sampling sessions subjects remained indoors under low light conditions and hourly urine samples were collected from 19:00 to 02:00 h. Samples were subsequently assayed for UaMT6s using standard radioimmunographic techniques. UaMT6s-onset was determined by the time at which melatonin production exceeded the average of three proceeding trials by 100%. Sleep onset times were derived from sleep diary and actigraphic measures taken before the melatonin collection nights. We found that there was no significant variation between nights in group mean UaMT6s-onset times, and intraindividual variability was small. In addition, UaMT6s-onset times were highly and significantly correlated between nights (grand mean r = 0.804). Our results suggest that within 95% confidence interval limits, individual UaMT6s-onset estimates obtained from a single night UaMT6s-onset study can be used to predict subsequent UaMT6s-onset times within +/- 97 min. A close temporal relationship was also found between the timing of UaMT6s-onset and sleep onset. Overall, our results suggest that under entrained conditions single-session UaMT6s-onset studies can provide reliable individual UaMT6s-onset phase estimates and that the protocol described in this study is a practical and noninvasive methodology.     

Biorhythmic variations in consciousness and psychological functions.

Research indicates that indices of conscious awareness of external and internal events exhibit both ultradian approximately 90-100 min (in adulthood) and circadian 24-hr variations. The phylogenetically older ultradian rhythm represents the basic rest-activity cycle (BRAC) of N. Kleitman (1963), is continuous, and appears to contain alternation of mental activity of thought-like and fantasy type at this periodicity in wakefulness and in NREM and REM sleep. This suggests continuous cyclic alternation of relative predominance of the left and right hemispheres inherent in the BRAC. Superimposed circadian fluctuations of consciousness in a diurnally active adult typically show lowest levels in the 1st hrs after usual sleep onset and a later dip at about 5-6:00 AM if the person remains awake. After a night of sleep, daytime consciousness and performance improve in the morning, usually show an early afternoon "post-lunch dip," a sustained increase in the late afternoon and early evening, and a decrease before sleep onset. It is postulated that cortical, mainly prefrontal, hyperpolarization in NREM sleep resets the cortex for renewed high-level perceptual awareness the next day. Consciousness is not a static attribute but shows definite biorhythmic fluctuations in level and type. (French abstract) (41/2 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sleep deprivation in adolescents and adults: Changes in affect.

The present study investigated the impact of sleep deprivation on several aspects of affective functioning in healthy participants selected from three different developmental periods: early adolescence (ages 10–13), midadolescence (ages 13–16), and adulthood (ages 30–60). Participants completed an affective functioning battery under conditions of sleep deprivation (a maximum of 6.5 hours total sleep time on the first night followed by a maximum of 2 hours total sleep time on the second night) and rest (approximately 7–8 hours total sleep time each night for two consecutive nights). Less positive affect was observed in the sleep-deprived, compared to rested, condition. This effect held for 9 of the 12 positive affect items on the PANAS-C. Participants also reported a greater increase in anxiety during a catastrophizing task and rated the likelihood of potential catastrophes as higher when sleep deprived, relative to when rested. Early adolescents appraised their main worry as more threatening when sleep deprived, relative to when rested. These results support and extend previous research underscoring the adverse affective consequences of sleep deprivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mood and sleep in aging women.

Examined the possible covariations of mood and sleep in a 5-yr follow-up of 25 normal, aging women (aged 56–66 yrs) who had originally participated in the 2nd author's (1982) study. Ss slept in the laboratory for 4 nights. Wiring for EEG recording began at 10:00 PM and a mood inventory was administered at 10:30 PM on the last 3 nights. Ss went to sleep at 11:00 PM, and EEG recording was continuous from bedtime until wake-up the following morning. Results show that mood assessments were independently related to both before and after sleep night. Only 2 sleep variables, sleep efficiency and latency to 1st REM period, were reliably related to daytime moods. The relative paucity of relation between mood and sleep variables was interpreted as reflecting a general insulation of sleep from day-to-day mood variations. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ropinirole for restless legs syndrome

Restless legs syndrome (RLS) is a common and underdiagnosed condition that results in a desire to move the extremities often associated with paresthesia/dysesthesia, motor restlessness, worsening of symptoms at rest with at least temporary relief by activity, and worsening of symptoms in the evening or night. We tested the new dopamine agonist ropinirole in 16 patients with RLS in an open-label trial. The mean daily dose was 2.8+/-2.3 mg (range, 0.5-12.0). The 13 patients who completed the study reported a 58.7% improvement (p = 1.08 x 10(-8)) as judged by the abbreviated International Restless Legs Study Group questionnaire. Three patients discontinued the medication secondary to adverse events (rash and nervousness) and other extenuating circumstances. These encouraging preliminary results justify larger and more controlled trials of ropinirole in patients with RLS.     

Cerebral hemodynamic changes in sleep apnea syndrome and effect of continuous positive airway pressure treatment

BACKGROUND AND OBJECTIVE: A clear association among snoring, sleep apnea, and increased risk of stroke has been shown by previous studies. However, the possible role played by sleep apnea in the pathogenesis of cerebrovascular disease is subject to debate. To evaluate the influence of hemodynamic changes caused by obstructive sleep apnea syndrome (OSAS), we investigated cerebrovascular reactivity to hypercapnia in patients with OSAS. METHODS: The study was performed at baseline and after 1 night and 1 month of nasal continuous positive airway pressure (n-CPAP) therapy, with patients in the waking state (8:00 to 8:30 AM and 5:30 to 6:00 PM) with transcranial Doppler ultrasonography. Cerebrovascular reactivity was calculated with the breath-holding index (BHI). RESULTS: In the baseline condition, compared with normal subjects, patients with OSAS showed significantly lower BHI values in both the morning (0.57 versus 1.40, p < 0.0001) and the afternoon (1.0 versus 1.51, p < 0.0001). Cerebrovascular reactivity was significantly higher in the afternoon than it was in the morning in both patients (p < 0.0001) and controls (p < 0.05). In patients, the BHI returned to normal values, comparable with those of control subjects, after both 1 night and 1 month of n-CPAP therapy. CONCLUSIONS: These findings suggest an association between OSAS and diminished cerebral vasodilator reserve. This condition may be related to the increased susceptibility to cerebral ischemia in patients with OSAS, particularly evident in the early morning.     

Use of angiotensin-converting enzyme inhibitors as monotherapy and in combination with diuretics and calcium channel blockers

This study presents results on sleep maturation during the first two years of life, based on a longitudinal study of 15 normal children recorded at home over 24 hours at the ages of 3, 6, 9, 12, 18 and 24 months. The development of the different stages and parameters of sleep was studied in quantitative, structural and circadian terms. To do so, various analyses were performed on the polygraphic recording data interpreted using the "adult" criteria suggested by Rechtschaffen et Kales in 1968. Results show the very early presence of some adult sleep parameters, such as the stable mean duration of episodes of paradoxical sleep (PS), the rapid decrease in the amount of this sleep stage, which reaches adult levels by the age of 9 months, the large amount of slow wave sleep in the first sleep cycle from the age of 3 months and the stability of the acrophase of the PS circadian rhythm. The position of the acrophase corresponds to the period of high PS density at the end of the night in adults. Other parameters, such as the increase in stages 1 and 2 of slow wave sleep, the increase in the latency of PS with disappearance at 9 months of PS onset, and the increase in stability of sleep with a decrease in nocturnal waking and body movements, are related to the maturation of the central nervous system structures implicated in the mechanisms of sleep (maturation of the thalamo-cortical pathways and the rostro-caudal pons-thalamus connections). These maturation processes may be markedly influenced by the environment. Finally, the increase with age in the amplitude of the sleep circadian rhythm may lead to both lengthening of the sleep cycle at the age of 12 months and development of the homeostatic process of sleep analysed by temporal changes in slow wave sleep.     

Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers

BACKGROUND: The purpose was to examine the effect of the antidepressant drug venlafaxine on sleep architecture and periodic leg movements of sleep (PLMS) in normal volunteers. METHOD: Eight normal volunteers were studied under laboratory sleep conditions as follows: 1 acclimatization night, 1 baseline night, and 4 consecutive nights of venlafaxine p.o. administration (75 mg during the first 2 nights and 150 mg the last 2 nights). RESULTS: Venlafaxine increased both wake time and sleep stage I. Sleep stages II and III were reduced. REM sleep time was reduced after the first venlafaxine dose, and, by the fourth night, REM sleep was completely suppressed in all volunteers. Six of the eight volunteers showed PLMS at a frequency above 25 per hour. CONCLUSION: Venlafaxine produces several sleep disturbances, which include abnormal leg movements.